August 6, 2014

New Discovery About Potential Genetic Predictor Of Stress

Everyone feels stressed out at times; however, for some stress evolves into mental and physical illnesses that lead to even worse illnesses and issues. For these reasons, scientists and doctors have long studied stress looking at what causes stress, how stress affects people, and what can be done to prevent and/or treat stress-related illnesses.

On Saturday, the University of Texas Health Science Center at San Antonio (UTHSC) released information about one study’s findings on a potential new predictor of stress-related disorders.

Stress often leads to depression, and the scientists involved in the UTHSC study that focused on depression in teens discovered that subtle changes in a gene predict the brain’s reaction to stress.

In addition to depression, stress can lead to post-traumatic stress disorder (PTSD) and obesity, which means understanding how to predict the brain’s reaction to stress may help lower these risks in the future.

For some time, scientists have believed that stress-related disorders are likely inherited or a result of exposure to traumatic events.

The UTHSC study, led by Dr. Douglas E. Williamson, in conjunction with studies from Duke University, Columbia University, and the University of Pittsburgh, focused on how genes change over time, which just might prove how those with the same genetic makeup are more susceptible to stress than others, particularly when that genetic makeup is prone to stress-related illnesses.

To connect genes and stress, researchers focused on the serotonin transporter. The serotonin transporter is a gene that regulates how much serotonin is signaled between brain cells. They used four methods to study the gene: fMRI, saliva tests, blood tests, and examining the brain tissue of deceased individuals. In focusing on this gene, they were able to prove “the existence of a mechanism impacting the brain that also may play a role in an individual’s reaction to stress, which may be a stronger predictor of stress than DNA sequencing.”

By performing an MRI, researchers at the University of Texas School of Medicine were able to look at the chemical marks through DNA methylation (a form of gene modification) of the serotonin transporter’s DNA, which shows when, where, and how much of a gene is expressed. By looking at the chemical marks scientists learned just how the same genetic code leads to such variety in the cellular responses. They could also focus on the differences in reactions to stress in individuals of both the same genetic makeup and of differing genetic makeup.

With the DNA methylation, “Varying the DNA sequence in this gene has been shown to predict activation in the amygdala and is linked with depression, so we were interested in determining if DNA methylation may be playing a role in regulating how the brain responds to stress, ultimately making an individual vulnerable to stress-related disorders like depression,” said Dr. Williamson.

From there, the researchers looked at brain images and saliva tests of 80 participants from Duke University. These study participants looked at angry or fearful faces while the study researchers recorded how the amygdala responded based on the brain images. In conjunction with Columbia University, researchers studied the 80 participants’ saliva samples measuring the amount of the genetic modification that took place on the serotonin transporter DNA. Scientists found that small changes in this DNA showed a direct correspondence to amygdala activity. This correspondence as well as the amount of methylation just might be the better predictor of stress-related disorders.

In order to prove this, the scientists needed researchers from the University of Pittsburgh. At this point in the study, they focused on analyzing DNA methylation and gene expression in brains from those who had passed away. In doing so, the researchers found the exact same results. As Dr. Williamson said, “The methylation sites on the fMRI images corresponded perfectly with lower levels of the serotonin transporter expression in the amygdala. Methylation was suppressing the expression of the gene.”

Ultimately, the researchers came to two conclusions:

1. The methylation patterns may be passed down through generations; and

2. Exposure to stress over time may impact changes in the methylation as well.

Understanding what predictors may lead to stress-related illnesses will better inform scientists, doctors, and patients so that all may work together in order to lower the risk of developing depression, PTSD, obesity, and other stress-related disorders.

Results of this research were published online Aug. 2 in the journal Nature.